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Regulation of autophagy by the nuclear factor κB signaling pathway in the hippocampus of rats with sepsis

BACKGROUND: Sepsis with brain dysfunction has contributed to an increase risk of morbidity and mortality. In its pathophysiology, both autophagy and nuclear factor κB (NF-κB) have been suggested to play important roles. Based on the fact that crosstalk between autophagy and NF-κB, two stress-respons...

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Autores principales: Su, YunJie, Qu, Yi, Zhao, FengYan, Li, HuaFeng, Mu, DeZhi, Li, XiHong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472259/
https://www.ncbi.nlm.nih.gov/pubmed/26067996
http://dx.doi.org/10.1186/s12974-015-0336-2
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author Su, YunJie
Qu, Yi
Zhao, FengYan
Li, HuaFeng
Mu, DeZhi
Li, XiHong
author_facet Su, YunJie
Qu, Yi
Zhao, FengYan
Li, HuaFeng
Mu, DeZhi
Li, XiHong
author_sort Su, YunJie
collection PubMed
description BACKGROUND: Sepsis with brain dysfunction has contributed to an increase risk of morbidity and mortality. In its pathophysiology, both autophagy and nuclear factor κB (NF-κB) have been suggested to play important roles. Based on the fact that crosstalk between autophagy and NF-κB, two stress-response signaling pathways, has been detected in other pathophysiological processes, this study was undertaken to explore the process of autophagy in the hippocampus of septic rats and the role NF-κB plays in the regulation of autophagy during the process. METHODS: Cecal ligation and puncture (CLP) or a sham operation was conducted on male Wistar rats. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of the NF-κB signaling pathway, or a vehicle control, was used to treat with the rats 2 h before the CLP operation. Hematoxylin-eosin staining and biological signal recording was used to measure the morphological and physiological signs of hippocampal dysfunction. An electron microscope was used to observe autophagosome formation and lysosome activation in the hippocampus after CLP. Western blotting and immune histochemistry were used to detect the hippocampus levels of NF-κB and essential proteins involved in formation of the autophagosome (microtubule-associated protein light chain 3 (LC3), Beclin1, Lamp-1, and Rab7). RESULTS: Compared with sham-operated rats, the CLP rats showed decreasing mean arterial pressure (MAP), increasing heart rate (HR), and pathological histological changes. CLP rats exhibited not only increased vacuolization through electron micrographs but also increased LC3-II, decreased Beclin1, LAMP-1, and Rab7 through the immunofluorescence and Western blot. However, PDTC + CLP rats revealed that inhibition of the NF-κB signal axis by PDTC increased the levels of LC3-II, Beclin1, LAMP-1, and Rab7 and improved physiological function including blood pressure and heart rate. CONCLUSIONS: The autophagy process during the hippocampus of CLP rats might be blocked by the activation of NF-κB signaling pathway. Inhibition of NF-κB signaling pathway could enhance the completion of autophagy with a neuroprotective function in septic brains.
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spelling pubmed-44722592015-06-19 Regulation of autophagy by the nuclear factor κB signaling pathway in the hippocampus of rats with sepsis Su, YunJie Qu, Yi Zhao, FengYan Li, HuaFeng Mu, DeZhi Li, XiHong J Neuroinflammation Research BACKGROUND: Sepsis with brain dysfunction has contributed to an increase risk of morbidity and mortality. In its pathophysiology, both autophagy and nuclear factor κB (NF-κB) have been suggested to play important roles. Based on the fact that crosstalk between autophagy and NF-κB, two stress-response signaling pathways, has been detected in other pathophysiological processes, this study was undertaken to explore the process of autophagy in the hippocampus of septic rats and the role NF-κB plays in the regulation of autophagy during the process. METHODS: Cecal ligation and puncture (CLP) or a sham operation was conducted on male Wistar rats. Pyrrolidine dithiocarbamate (PDTC), an inhibitor of the NF-κB signaling pathway, or a vehicle control, was used to treat with the rats 2 h before the CLP operation. Hematoxylin-eosin staining and biological signal recording was used to measure the morphological and physiological signs of hippocampal dysfunction. An electron microscope was used to observe autophagosome formation and lysosome activation in the hippocampus after CLP. Western blotting and immune histochemistry were used to detect the hippocampus levels of NF-κB and essential proteins involved in formation of the autophagosome (microtubule-associated protein light chain 3 (LC3), Beclin1, Lamp-1, and Rab7). RESULTS: Compared with sham-operated rats, the CLP rats showed decreasing mean arterial pressure (MAP), increasing heart rate (HR), and pathological histological changes. CLP rats exhibited not only increased vacuolization through electron micrographs but also increased LC3-II, decreased Beclin1, LAMP-1, and Rab7 through the immunofluorescence and Western blot. However, PDTC + CLP rats revealed that inhibition of the NF-κB signal axis by PDTC increased the levels of LC3-II, Beclin1, LAMP-1, and Rab7 and improved physiological function including blood pressure and heart rate. CONCLUSIONS: The autophagy process during the hippocampus of CLP rats might be blocked by the activation of NF-κB signaling pathway. Inhibition of NF-κB signaling pathway could enhance the completion of autophagy with a neuroprotective function in septic brains. BioMed Central 2015-06-12 /pmc/articles/PMC4472259/ /pubmed/26067996 http://dx.doi.org/10.1186/s12974-015-0336-2 Text en © Su et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Su, YunJie
Qu, Yi
Zhao, FengYan
Li, HuaFeng
Mu, DeZhi
Li, XiHong
Regulation of autophagy by the nuclear factor κB signaling pathway in the hippocampus of rats with sepsis
title Regulation of autophagy by the nuclear factor κB signaling pathway in the hippocampus of rats with sepsis
title_full Regulation of autophagy by the nuclear factor κB signaling pathway in the hippocampus of rats with sepsis
title_fullStr Regulation of autophagy by the nuclear factor κB signaling pathway in the hippocampus of rats with sepsis
title_full_unstemmed Regulation of autophagy by the nuclear factor κB signaling pathway in the hippocampus of rats with sepsis
title_short Regulation of autophagy by the nuclear factor κB signaling pathway in the hippocampus of rats with sepsis
title_sort regulation of autophagy by the nuclear factor κb signaling pathway in the hippocampus of rats with sepsis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4472259/
https://www.ncbi.nlm.nih.gov/pubmed/26067996
http://dx.doi.org/10.1186/s12974-015-0336-2
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